AIDS virus reformatted to shuttle repair genes to diseased brains

Scientists supported by the National Institutes of Health (NIH) have developed a benign, reconstituted form of HIV, the virus known to cause AIDS, and used it to shuttle repair genes to diseased neurons in rat brains. By removing any trace of the part of HIV that would allow it to replicate itself and become infectious (and thus lethal) and using only the part that can integrate itself into a host's gene sequence, the researchers were able to insert the reformatted HIV into non-dividing cells, specifically neurons, in the brains of rats.

Dr. Fred Gage, one of the three laboratory chiefs at the Salk Institute in La Jolla, Calif., where the discovery was made says, "The basic knowledge we have gleaned of how HIV infects cells has enabled us to develop a reconstituted HIV 'delivery system' for diseased neurons -- it is truly a case of turning swords into plowshares. Using a virus delivery system offers hope for successful gene therapy in many life-threatening diseases such as cystic fibrosis, muscular dystrophy and perhaps even Alzheimer's disease." The finding is reported in the April 12, 1996 issue of Science.

The ability to insert genetic material that may carry helpful information into genetic locations associated with diseases such as Parkinson's is a hallmark of gene therapy. This study is one of the first to show a workable model in animals that targets nerve cells. Gage's work was funded by the National Institute on Aging (NIA). His co-workers at the Salk Institute are Drs. Inder M. Verma and Didier Trono. Dr. Trono was funded by the National Institute of Allergy and Infectious Diseases (NIAID).

The initial breakthrough in this research came when Drs. Verma and Trono's labs extensively "debilitated" HIV and, using a protein piece from another virus, created very efficient viral vectors. Viral vectors are essentially microscopic shuttles which, by virtue of their stealth capabilities, carry genes to targeted cells. According to Dr. Trono, "The beauty of this vector is that healing genes can be delivered directly into the body, without cumbersome manipulations of the patients' cells in vitro. Genes can be introduced into targets such as neurons, which have previously been beyond the reach of many vectors. An additional benefit of this vector is that it does not trigger toxic immune reactions as other vectors have been known to do."

As proof of the effectiveness of Drs. Verma and Trono's vectors, Dr. Gage's lab introduced the recombinant HIV vectors into five female adult rat brains and showed that foreign genes carried by the shuttle vectors could be efficiently inserted into genes in a brain's neurons. The transferred product was detectable in the rat brains for at least a month.

Gage and his co-worker, Dr. Ulrike Blomer, who performed their work in live rats, suggest that if human testing is done, cow or monkey variants of HIV should be used to avoid any possibility of human infection with HIV. Gage says "This science is a great example of melding two areas of basic research -- neurology and virology -- and using a substance like HIV to actually work to the good and not the ill."

The National Institute on Aging leads the Federal effort supporting basic, clinical, epidemiological, and behavioral research on aging and the special needs of older people. The National Institute of Allergy and Infectious Diseases conducts and supports research to prevent, diagnosis, and treat illnesses such as AIDS and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIA and NIAID are both components of the National Institutes of Health, an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.